October 2, 2012

Similarities And Differences Found In Bird And Mammalian Neocortex

Humans and other mammals have a seemingly unique part of the brain called the neocortex, which is a layered structure on the outer surface where higher-order processing is thought to occur. A new study from the University of Chicago found similar cells in the brains of birds, but in a vastly different anatomical structure.

Confirming a 50-year hypothesis about the identity of a mysterious structure in the bird brain, the new study sheds light on the evolution of the brain and opens new animal models for studying the neocortex.

"If you want to study motor neurons or dopamine cells, which are biomedically important, you can study them in mammals, in chick embryos, in zebrafish. But for these neurons of the cerebral cortex, we could only do that in mammals before," said Clifton Ragsdale, PhD, associate professor of neurobiology at University of Chicago Division of Biological Sciences and senior author of the study. "Now, we can take advantage of these other experimental systems to ask how they are specified, can they regenerate, and other questions."

The neocortex-like structure in the bird brain is called the dorsal ventricular ridge (DVR). Both the DVR and the mammalian neocortex originate from an embryonic region called the telencephalon, but they mature into very different shapes. The neocortex is made up of six distinct cortical layers while the DVR contains large clusters of neurons called nuclei.

This divergence in anatomy causes many scientists to propose that the bird DVR doesn't correspond to the mammalian cortex, but rather the amygdala.

"All mammals have a neocortex, and it's virtually identical across all of them," said Jennifer Dugas-Ford, PhD, postdoctoral researcher at the University of Chicago and first author on the paper. "But when you go to the next closest group, the birds and reptiles, they don't have anything that looks remotely similar to neocortex."

Neuroscientist Harvey Karten researched the neural inputs and outputs of the DVR in the 1960's. He found that they were remarkably like the pathways traveling to and from the neocortex in mammals. Despite the dramatically different anatomy, Karten proposed that the DVR performs similar functions to the neocortex.

The research team tested Karten's hypothesis by using recently discovered sets of molecular markers that identify specific layers of mammalian cortex. These are the layer 4 "input" neurons or the layer 5 "output" neurons. The team looked at the DVR to see if these same marker genes were expressed in the DVR nuclei.

In the chicken finch and the zebra finch, the team found that level 4 and level 5 markers were expressed by distinct nuclei of the DVR. This supports Karten's hypothesis that the DVR cells are homologous to those of the mammalian neocortex.

"Here was a completely different line of evidence," Ragsdale said. "There were molecular markers that picked out specific layers of cortex; whereas the original Karten theory was based just on connections, and some people dismissed that. But in two very distant birds, all of the gene expression fits together very nicely with the connections."

"All of our markers were exactly where they thought they would be in the DVR when you're comparing them to the neocortex," Dugas-Ford said.

A second experiment was conducted on a species of turtle, revealing another anatomical possibility for these neocortex-like cells. The turtle brain had layer 4- and 5-like cells along a single layer of the species dorsal cortex instead of a six-layer neocortex or a cluster of nuclei.

"I think that's the interesting part, that you can have all these different morphologies built with the same cell types, just in different conformations," Rowell said. "It's a neocortex or a big clump of nuclei, and then in reptiles they have an unusual dorsal cortex unlike either of those."

The team is planning future experiments to test the developmental steps that shape these neurons into various structures, and the pros and cons of these anatomical differences. Some bird species have complex language and tool-usage, which suggests that the nuclear organization of this pathway is capable of supporting advanced functions. It may even offer advantages over the mammalian brain.

"If you wanted to have a special nuclear processing center in Broca's area to carry out language processing, you can't do that in a mammal," Ragsdale said. "But in a bird they have these special nuclei that are involved in vocalization. It's as if you have additional flexibility: You can have shorter circuits, longer circuits, you can have specialized processing centers."

The discovery of homologous neocortex cell types will allow scientists to study cortical neurons in bird species such as the chicken. The chicken is used as a common model for examining embryonic development. Such research could help scientists more easily study the neurons lost in paralysis, deafness, blindness and other neurological conditions.